crossing96/oncoscreening huggingface dataset:
NCAPH promotes cell proliferation and inhibits cell apoptosis of bladder cancer cells through MEK/ERK signaling pathway.	Bladder cancer (BC) is one of the most common cancers world-wide with a poor prognosis. Non-SMC (Structural Maintenance of Chromosomes)-condensin I complex subunit H (NCAPH) is a regulatory subunit of the condensin I complex and plays an important role in tumorigenesis and progression in several types of cancers. However, the role of NCAPH in BC remains unknown. In this study, we tried to reveal the biological functions of NCAPH in BC. We detected the expressions of NCAPH in BC and adjacent tissues, and BC cells lines. Subsequently, the gain- and loss-of-function experiments were performed to determine the effects of NCAPH on BC cell proliferation, apoptosis, and activation of the MEK/ERK signaling pathway in vitro. Moreover, we used BALB/c nude mice and established a xenograft model to investigate whether silence NCAPH using shRNA targeting NCAPH (shNCAPH) can inhibit BC tumor growth in vivo. The results showed NCAPH was overexpressed in BC tissues compared to adjacent tissues and highly expressed in BC cell lines. Additionally, overexpression of NCAPH promoted cell proliferation and inhibited apoptosis in SW780 cells. Conversely, knockdown of NCAPH reduced cell proliferation and enhanced apoptosis in UMUC3 cells. Furthermore, we found that the NCAPH activated the MEK/ERK signaling pathway in BC cells. MEK1/2 inhibitor U0126 blocked the increase of cell proliferation regulated by NCAPH overexpression. Knockdown of NCAPH significantly inhibited tumor growth in mice. Our results suggest that NCAPH might play an important role in BC progression and provide the potential marker in the diagnosis of BC.	bladder
Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis.	BACKGROUND: The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan. METHODS: Patients with locally advanced or metastatic UC that had not progressed with 4-6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and safety. RESULTS: In Japanese patients (n = 73) randomized to avelumab + BSC (n = 36) or BSC alone (n = 37), median OS was 24.7 months (95% CI, 18.2-not estimable) vs 18.7 months (95% CI, 12.8-33.0), respectively (HR, 0.81 [95% CI, 0.41-1.58]), and median PFS was 5.6 months (95% CI, 1.9-9.4) vs 1.9 months (95% CI, 1.9-3.8), respectively (HR, 0.63 [95% CI, 0.36-1.11]). In the avelumab + BSC and BSC-alone arms, grade ≥ 3 treatment-emergent adverse events (AEs) occurred in 50.0% vs 8.1%, including grade ≥ 3 treatment-related AEs in 13.9% vs 0%, respectively. Efficacy and safety results in Japanese patients were generally consistent with findings in the overall trial population. CONCLUSION: Avelumab 1L maintenance treatment showed a favorable benefit-risk balance in Japanese patients, supporting avelumab 1L maintenance as a new standard of care in Japanese patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02603432.	bladder
TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6.	Urinary bladder carcinoma refers to the commonest carcinoma with weak prognostic result for the patient as impacted by the limited treatment possibilities and challenging diagnosing process. Nevertheless, the molecular underpinning of bladder carcinoma malignant progression is still not clear. As a novel core part of pluripotency circuitry, testicular expression 10 (TEX10) plays an actively noticeable effect on reprogramming, early embryo development, and embryonic stem cell self-renewal. Nevertheless, TEX10 expressions and functions within bladder carcinoma are still not known. The present work is aimed at revealing TEX10 expression and biological function within urinary bladder carcinoma and elucidating the potential mechanisms. Results showed that TEX10 is abundant in urinary bladder carcinoma, and its protein level was related to poor disease-free survival in a positive manner. Reduced TEX10 level inhibited urinary bladder carcinoma cell proliferating process and metastasis in vitro and xenograft tumorigenicity in vivo. Notably, TEX10 might regulate carcinoma cell proliferating process and metastasis via XRCC6, thereby controlling the signaling of Wnt/β-catenin and DNA repair channel. Moreover, TEX10 gene knockout reduced the radiotherapy resistance of urinary bladder carcinoma. In brief, this work revealed that TEX10 could exert a significant carcinogenic effect on urinary bladder carcinoma tumorigenesis and radiotherapy resistance through the activation of XRCC6-related channels. Accordingly, targeting TEX10 is likely to offer a novel and feasible therapeutically related strategy for inhibiting urinary bladder carcinoma tumorigenicity.	bladder
Identification of Genetic Risk Factors for Familial Urinary Bladder Cancer: An Exome Sequencing Study.	PURPOSE: Previous studies have shown an approximately two-fold elevation in the relative risk of urinary bladder cancer (UBC) among people with a family history that could not be entirely explained by shared environmental exposures, thus suggesting a genetic component in its predisposition. Multiple genome-wide association studies and recent gene panel sequencing studies identified several genetic loci that are associated with UBC risk; however, the list of UBC-associated variants and genes is incomplete. MATERIALS AND METHODS: We exome sequenced eight patients from three multiplex UBC pedigrees and a group of 77 unrelated familial UBC cases matched to 241 cancer-free controls. In addition, we examined pathogenic germline variation in 444 candidate genes in 392 The Cancer Genome Atlas UBC cases. RESULTS: In the pedigrees, segregating variants were family-specific although the identified genes clustered in common pathways, most notably DNA repair (MLH1 and MSH2) and cellular metabolism (IDH1 and ME1). In the familial UBC group, the proportion of pathogenic and likely pathogenic variants was significantly higher in cases compared with controls (P = .003). Pathogenic and likely pathogenic variant load was also significantly increased in genes involved in cilia biogenesis (P = .001). In addition, a pathogenic variant in CHEK2 (NM_007194.4:c.1100del; p.T367Mfs*15) was over-represented in cases (variant frequency = 2.6%; 95% CI, 0.71 to 6.52) compared with controls (variant frequency = 0.21%; 95% CI, 0.01 to 1.15), but was not statistically significant. CONCLUSION: These results point to a complex polygenic predisposition to UBC. Despite heterogeneity, the genes cluster in several biologically relevant pathways and processes, for example, DNA repair, cilia biogenesis, and cellular metabolism. Larger studies are required to determine the importance of CHEK2 in UBC etiology.	bladder
Impact of Variant Histology on Occult Nodal Metastasis after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Review of the National Cancer Database.	Up to 14% of bladder urothelial carcinoma has variant histology (VH), which is associated with a higher incidence of occult regional lymph node metastasis. Neoadjuvant chemotherapy (NAC) is the gold-standard for resectable cT2-4 disease as it achieves pathologic complete response (pCR) in select patients at the time of radical cystectomy (RC). A landmark trial demonstrated chemosensitivity and pT0 status in the setting of VH. pT0N+ pathology in patients undergoing subsequent RC has prompted concerns about post-chemotherapy bladder preservation. We investigate how VH impacts pathologic primary site and nodal downstaging post-NAC. We queried the National Cancer Database for cT2-4N0M0 patients who underwent NAC and RC between 2004 and 2016. These patients were stratified into pure urothelial cell carcinoma (UCC) and VH. The rate of downstaging to ≤pT1 was analyzed, along with pN+ status. Overall survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model. Multivariable models were adjusted for demographic and clinicopathologic variables. Of 5,335 patients, 92.1% were UCC and 7.9% VH. UCC was associated with better unadjusted survival and lower adjusted odds of being pN+ (aOR = 0.60, P < .001). Squamous cell, glandular, and sarcomatoid histologies were significantly associated with decreased adjusted odds of any pT downstage. Neuroendocrine histology (NE) trended towards increased adjusted odds of downstage to pT0N0. Patients with VH were more likely to harbor occult regional lymph node metastasis in the setting of intravesical pCR. NE had the highest pT0N0 rate, with potential implications on post-NAC bladder preservation. These findings reinforce the role of RC after NAC especially for VH.	bladder
Nutritional Status Impairment Due to Neoadjuvant Chemotherapy Predicts Post-Radical Cystectomy Complications.	BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer (MIBC). Neoadjuvant chemotherapy (NAC) is associated with improved patient survival. The impact of NAC on nutritional status is understudied, while the association between malnutrition and poor surgical outcomes is well known. This study aims to examine the association between NAC, nutritional status impairment, and post-operative morbidity. MATERIALS AND METHODS: We included MIBC patients who underwent RC and received NAC from multiple academic centers in Israel. Cross-sectional imaging was used to measure the psoas muscle area and normalized it by height (smooth muscle index, SMI). Pre- and post-NAC SMI difference was calculated (represents nutritional status change). The primary outcomes were post-RC ileus, infection, and a composite outcome of any complication. Logistic regression models were fit to identify independent predictors of the outcomes. RESULTS: Ninety-one patients were included in the study. The median SMI change was -0.71 (-1.58, -0.06) cm(2)/m(2). SMI decline was significantly higher in patients with post-RC complications (-18 vs. -203, p < 0.001). SMI change was an independent predictor of all complications, ileus, infection, and other complications. The accuracy of SMI change for predicting all complications, ileus, infection, and other complications was 0.85, 0.87, 0.75, and 0.86, respectively. CONCLUSIONS: NAC-related nutritional deterioration is associated with increased risk of complications after RC. Our results hint towards the need for nutritional intervention during NAC prior to RC.	bladder
International Bladder Cancer Group Consensus Statement on Clinical Trial Design for Patients with Bacillus Calmette-Guérin-exposed High-risk Non-muscle-invasive Bladder Cancer.	CONTEXT: A large proportion of patients with non-muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design. OBJECTIVE: To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease. EVIDENCE ACQUISITION: We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in ClinicalTrials.gov as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC. EVIDENCE SYNTHESIS: BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided. CONCLUSIONS: The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state. PATIENT SUMMARY: Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.	bladder
Metastatic Breast Carcinoma Mimicking Urothelial Carcinoma.	Besides being the most frequently diagnosed cancer in women, breast cancer is the main cause of cancer-related deaths in this group of patients. Breast cancer frequently metastasizes to bone, lung, brain, and liver. Renal metastasis from the breast is extremely rare. Here we aimed to report a case of breast cancer with metastasis to bone and left renal pelvis. A 58-year old woman with a mass lesion in the left renal pelvis that mimicked urothelial carcinoma was referred to our clinic. The left nephroureterectomy procedure was performed, and the pathology revealed that a renal pelvis metastasis secondary to breast cancer.	bladder
En bloc resection for nonmuscle-invasive bladder cancer: selecting a proper laser.	PURPOSE OF REVIEW: To discuss the most recent surgical lasers that have been made available to us and to evaluate their potential in performing en bloc resection of nonmuscle invasive bladder cancer. RECENT FINDINGS: Laser en bloc resection of bladder tumors (ERBT) can be performed with a number of laser systems including Ho:YAG, GreenLight, diode, Tm:YAG and thulium fiber lasers (TFL). The data that is currently available suggests that the water-targeting devices (utilizing water as a primary chromophore - Ho:YAG, Tm:YAG, TFL) may have a number of advantages over hemoglobin-targeting systems (potassium titanyl phosphate:YAG, lithium triborate:YAG). One recent addition to the surgical armamentarium Moses effect enhanced Ho:YAG and the TFL (being able to work both in quasi-continuous and SuperPulsed modes) necessitates careful discussion and comparison with the other available devices. SUMMARY: The majority of available lasers have proven to be safe to use and compared to electrocautery allow for lower rates of obturator nerve reflex and result in fewer bleeding complications. The minimal penetration depth and decreased peak power of Tm:YAG and TFLs render them the devices of choice when it comes to ERBT. Unfortunately, more studies on ERBT with TFL are needed in order for us to make a sound assessment of the respective pros and cons.	bladder
Race, ethnicity, and gender reporting in North American clinical trials for BCG-unresponsive non-muscle invasive bladder cancer.	INTRODUCTION: The National Institutes of Health (NIH) Revitalization Act of 1993 established guidelines for the inclusion of racial/ethnic minorities and women in clinical research. However, the reporting rate of such patient demographic data in clinical trials for BCG-unresponsive non-muscle invasive bladder cancer is not well characterized. METHODS: We identified published clinical trials of all phases (I -III) for BCG-unresponsive non-muscle invasive bladder cancer conducted in the US and/or Canada. We calculated the proportion of studies reporting patient gender and race/ethnicity, tabulating these data when present. We compared reported trial participant race, ethnicity and gender with the number of new bladder cancer cases and deaths using the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI) U.S. Cancer Statistics data from 2013 -2017. RESULTS: We identified 27 trials published from 1998 -2021 enrolling a total of 1673 patients. While all trials included data on patient gender (22% women overall), only 40.7% included any data on patient race/ethnicity. Among those that did, trial participants were reported as white (94%), Black (2.1%), Hispanic (0.6%), Asian (0.9%), and Other (2.3%). Racial/ethnic minorities were underrepresented in clinical trials relative to their proportion of new bladder cancer cases and deaths. CONCLUSION: Most clinical trials that have been conducted for BCG-unresponsive non-muscle invasive bladder cancer do not report data on patient race or ethnicity despite NIH guidelines advocating for inclusion of such data. Racial/ethnic minorities remain underrepresented in these trials relative to the burden of bladder cancer prevalence and mortality faced by these groups.	bladder
Berberine enhances gemcitabine‑induced cytotoxicity in bladder cancer by downregulating Rad51 expression through inactivating the PI3K/Akt pathway.	Although gemcitabine (GEM) has been used to treat bladder cancer (BC) for a number of years, severe adverse events or drug resistance frequently develops. A series of drugs have been proved to sensitize patients to GEM and reduce the side effects. The aim of the present study was to evaluate the potential effects of berberine (BER) on GEM‑induced cytotoxicity in BC and to explore the possible underlying mechanisms. T24 and 5637 human BC cell lines were treated with GEM and/or BER before cell proliferation, apoptosis and migration were studied. Oncomine databases and Gene Expression Profiling Interactive Analysis (GEPIA) were used to retrieve RAD51 recombinase (Rad51) mRNA expression. Overexpression plasmid or specific Rad51 small interfering RNA were used to examine the role of Rad51 in drug‑treated BC cells. BC model mice were administered with GEM and/or BER before changes in tumor volume, size and Ki67 expression were assessed. BER enhanced GEM‑induced cytotoxicity, apoptosis and inhibition of migration, whilst attenuating the GEM‑induced upregulation of phosphorylated Akt and Rad51 expression. According to Oncomine and GEPIA analyses, Rad51 was found to be significantly upregulated in BC tissues compared with that in normal tissues, where there was a weak positive correlation between Rad51 and Akt1 expression. Knockdown of Rad51 enhanced GEM‑induced cytotoxicity, whilst overexpression of Rad51 reversed the suppressed cell viability induced by BER and GEM. Inactivation of the PI3K/Akt pathway by LY294002 or BER enhanced GEM‑induced cytotoxicity and downregulated Rad51 expression, whilst overexpression of constitutively active Akt restored Rad51 expression and cell viability that was previously decreased by BER and GEM. BER additively inhibited tumor growth and Ki67 expression when combined with GEM in vivo. These results suggest that BER can enhance GEM‑induced cytotoxicity in BC by downregulating Rad51 expression through inactivating the PI3K/Akt pathway, which may represent a novel therapeutic target for BC treatment.	bladder
Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer.	BACKGROUND: The unfolded protein response (UPR) served as a vital role in the progression of tumors, but the molecule mechanisms of UPR in bladder cancer (BLCA) have been not fully investigated. METHODS: We identified differentially expressed unfolded protein response-related genes (UPRRGs) between BLCA samples and normal bladder samples in the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set. We implemented the validation of the prognostic signature in GSE13507 from the Gene Expression Omnibus database. The ESTIMATE, CIBERSORT, and ssGSEA algorithms were used to explore the correlation between the prognostic signature and immune cells infiltration as well as key immune checkpoints (PD-1, PD-L1, CTLA-4, and HAVCR2). GDSC database analyses were conducted to investigate the chemotherapy sensitivity among different groups. GSEA analysis was used to explore the potential mechanisms of UPR-based signature. RESULTS: A prognostic signature comprising of seven genes (CALR, CRYAB, DNAJB4, KDELR3, CREB3L3, HSPB6, and FBXO6) was constructed to predict the outcome of BLCA. Based on the UPRRGs signature, the patients with BLCA could be classified into low-risk groups and high-risk groups. Patients with BLCA in the low-risk groups showed the more favorable outcomes than those in the high-risk groups, which was verified in GSE13507 set. This signature could serve as an autocephalous prognostic factor in BLCA. A nomogram based on risk score and clinical characteristics was established to predict the over survival of BLCA patients. Furthermore, the signature was closely related to immune checkpoints (PD-L1, CTLA-4, and HAVCR2) and immune cells infiltration including CD8(+) T cells, follicular helper T cells, activated dendritic cells, and M2 macrophages. GSEA analysis indicated that immune and carcinogenic pathways were enriched in high-risk group. CONCLUSIONS: We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer.	bladder
Bladder Recurrence Following Diagnostic Ureteroscopy in Patients Undergoing Nephroureterectomy for Upper Tract Urothelial Cancer: Is Ureteral Access Sheath Protective?	OBJECTIVE: To examine the effect of diagnostic ureteroscopy (URS) and ureteral access sheath usage on bladder recurrence following radical nephroureterectomy (RNU). METHODS: We retrospectively reviewed the records of patients who underwent RNU between 2005 - 2019. Patients with a history of bladder cancer and those without a bladder cuff resection were excluded. Bladder recurrence was the primary outcome and cox regression modeling was used to assess the impact of URS adjusting for other factors. RESULTS: Out of 271 RNU cases, 143 were included with a median age of 73 years (IQR 65 - 80). URS was performed in 104 cases (73%) and a ureteral access sheath was used in 26 (25%). With a median follow-up of 27 months, there were 36 (25%) bladder recurrences. The bladder recurrence rate (median time to recurrence) for patients who had URS vs no URS was 30.8% (9.0 months) and 7.7% (12.1 months), respectively (P = .02). A lower recurrence rate was noted in patients whom a ureteral access sheath was utilized (11.5%) vs those with no access sheath (39.7%, P = .01). Multivariable analysis revealed a significant increase in bladder recurrence if URS was performed prior to RNU (HR 5.6 [1.7 - 18.5], P <.004), however, this effect was mitigated if a ureteral access sheath was used (HR 1.3, [0.3 - 6.4], P = .76). Ureteral stent usage and performing a ureteroscopic biopsy had no significant effect on bladder recurrence. CONCLUSION: Diagnostic URS in patients undergoing RNU for UTUC significantly increases the risk of bladder recurrence. This effect may be mitigated by using a ureteral access sheath.	bladder